Progress in curing prostate cancer could be greatly facilitated by identification of reliable and highly specific new serological markers for diagnostics and development of new therapeutic strategies and pharmaceuticals for effective elimination of prostate cancer cells. Both goals could be achieved through identification of new molecular targets for selective killing or selective detection of cancer cells of prostate origin. The present program is aimed at identification of prospective gene targets for both diagnostic and therapeutic applications using a combination of recently developed powerful functional gene cloning methodologies with cDNA array-based gene expression profiling and rationally designed experimental models. Diagnostic and therapeutic value of prospective candidates will be evaluated using specific inhibitors and antibodies. Aim 1 is devoted to identification of new candidate prostate tumor markers among proteins encoded by prostate-specific genes that are under negative control of tumor suppressor genes (PTEN, Rb, p53 and p27) followed by designing immunodiagnostic serological assay for prostate cancer. This approach is an extension of a recent work that linked tumor specificity of PSA expression with its negative regulation by p53. Aims 2 and 3 represent cells by small molecules. They are based on two new genetic methodologies recently developed by research the research team. Genetic elements specifically killing prostate carcinoma cells (with specific focus on hormone-independent tumors) will be isolated by functional screening of expression libraries of prostate-specific gene sequences collected based on a combination of experimental and bioinformatics-based criteria. Genes essential for viability of prostate cells (EVP-genes) will be defined and used as targets for selection of specific small molecules inhibiting growth of cells of prostate origin that will serve as prototype new drugs for prostate cancer treatment.